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This volume contains a collection of innovative techniques for studying targeted protein degradation. Chapters guide readers through heterobifunctional proteolysis-targeting chimeras (PROTACs) approaches, E3 ligase, E3 ligase-induced ubiquitylation, proteomic approaches, novel degrader molecules, molecular glue, and stabilize binding interaction between a target and E3 ubiquitin ligase. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Targeted Protein Degradation: Methods and Protocols aims to ensure successful results in this emerging field of drug discovery.
This volume contains a collection of innovative techniques for studying targeted protein degradation. Chapters guide readers through heterobifunctional proteolysis-targeting chimeras (PROTACs) approaches, E3 ligase, E3 ligase-induced ubiquitylation, proteomic approaches, novel degrader molecules, molecular glue, and stabilize binding interaction between a target and E3 ubiquitin ligase. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Targeted Protein Degradation: Methods and Protocols aims to ensure successful results in this emerging field of drug discovery.
The fast tempo decisive combat operations has been called the "New American Way of War." This is in contrast to the traditional "American Way of War" which emphasized using massive amounts of firepower in a "grinding strategy of attritions" like the United States did against Germany and Japan in World War II. A major problem for Joint Force commanders and their staffs is that the speed of campaign in this "New American Way of War" challenges their ability to adequately plan for both the decisive war fight and the transition to post conflict operations. Campaigns of attrition in the traditional "American Way of War" tended to be long and therefore there was time during the war fight to plan for the aftermath. Obviously, a solution to this problem is not to revert back to the attrition based strategy, but to figure out how to best organize our commands to deal with this planning complexity. There are many implications with this transition from war fighting to the post conflict across the echelons of command and levels of war from training of combat forces to the integration of the interagency into the operational concept. This monograph focuses on one such implication of this new American way of war, the ability for the command structure to adequately plan through the entire campaign. The monograph's thesis is to better facilitate the transition from the dominate phase to the stability phase will require separate operational-level headquarters, with sufficient training and expertise, focused on each of these phases working under a geographic combatant commander's overall operational design. In operational design, it is important to get the overall command structure right with appropriate levels of responsibility and clear relationships and objectives. An examination of three past operations will reveal insights on the validity of the hypothesis. The first case study is General Eisenhower's Supreme Headquarters'; Allied Expeditionary Force (SHAEF) in the European Thea
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